100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months

Other Name: Trimethoprim-Sulfamethoxazole Combination

Placebo Comparator: infant placebo

Drug: cotrimoxazole placebo

100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months

Active Comparator: exclusive breastfeeding for 6 months

Behavioral: exclusive breastfeeding until 6 months of age

Breastfeeding for 6 months, followed by formula feeding for 6 month. Breastfeeding infants will be prophylaxed with maternal highly active antiretroviral therapy (HAART) (if available) or with infant nevirapine.

Active Comparator: exclusive breastfeeding for 12 months

Behavioral: breastfeeding for 12 months

Breastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine.

Detailed Description:

As improved MTCT prevention interventions reduce the number of HIV-infected infants in the antepartum and peripartum periods, interventions to improve HIV-free survival among HIV-uninfected infants are needed. Morbidity and mortality are increased among HIV-uninfected infants born to HIV-infected mothers, and reduced infant survival among HIV-exposed infants may lead to as many deaths as HIV infection itself. In Botswana, the use of formula feeding or shorter breastfeeding may worsen the problem of early infant mortality among HIV-exposed infants.

The study will enroll pregnant or postpartum HIV-1-infected women, and their HIV-uninfected infants in Botswana. At 2-4 weeks of age, live HIV-uninfected infants will be randomized to receive either double-blinded cotrimoxazole (CTX) or placebo from 2-4 weeks through 15 months. In addition, breastfeeding (BF) infants will be randomized to BF until either 6 or 12 months of age. Children will be followed prospectively until 18 months of age. The primary endpoint will be survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of BF among those BF at randomization. Secondary endpoints will evaluate survival and morbidity/mortality at 12 and 15 months; HIV-free survival to 18 months; and the safety of CTX prophylaxis. Secondary observational objectives include comparing MTCT and mortality by initial feeding method (formula feeding or any BF > 1 month), and an analysis of maternal characteristics as predictors for initial feeding choice and HIV-free survival. All women and infants will receive standard antenatal and peripartum prophylaxis from the Botswana government for MTCT prevention (PMTCT), and will choose a feeding method with counseling. Breastfeeding infants will receive infant nevirapine (NVP) prophylaxis or will be protected from MTCT by the use of maternal HAART.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-infected women, > 26 weeks gestation and < 34 days postpartum.

Women must be ¬> 18 years of age and willing/able to sign informed consent.

Women and infants must be able to follow up regularly at a study clinic through 18 months postpartum.

For Feeding Randomization Only: Women must be willing to breastfeed for up to 12 months, and to stop at 6 months, depending upon their feeding assignment.

Exclusion Criteria:

Antepartum women: Known infant anomalies resulting in a high probability that the infant will not survive to 18 months.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01229761

Locations

Botswana

Princess Marina Hospital

Gaborone, Botswana

Athlone Hospital

Lobatse, Botswana

Scottish Livingstone Hospital

Molepolole, Botswana

Sponsors and Collaborators

Harvard School of Public Health

Harvard Medical School

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)